Biography
Biography: Paolo Lombardi
Abstract
Berberine is an isoquinoline quaternary plant alkaloid which has been used in the Ayurvedic and Chinese medicines since hundreds of years. The diverse pharmacological properties exhibited by berberine not only indicate that the alkaloid has a definite potential in a wide spectrum of clinical applications, but also that it represents an attractive natural lead compound by providing a biologically interesting skeleton for the introduction of chemical modifications in search for more selective and specific medical indications. Anticancer properties of berberine have also been reported and our studies identified berberine as a novel, non specific inhibitor of the nascent synthesis of some proteins, supposedly acting as a RNA silencing agent. In normal cells, signaling transduction pathways converge into several components of translational machinery. However, these components are often deregulated in cancer cells making the translated proteins becoming oncogenic. Accordingly, the appreciation of the differences in mRNA translational control between normal cells and cancerous cells makes it a possible therapeutic opportunity against cancer. In this respect we discovered novel 1, 3-diarylalkylberberine derivatives with improved anticancer properties. Several of the new berberine derivatives show remarkable anti-proliferative effects on a variety of human cancer cell lines which either acquired resistance or are normally refractory to chemotherapy. Although the precise molecular basis of the biological activities of berberine is still debated, at least for the anticancer activity we present new information and data regarding down regulation of cancer related protein expression as the putative major biological effect of this class of compounds which is exploitable for clinical applications. These new derivatives are believed to have the property to bind to oligonucleotides and to function as selecting suppressors of protein synthesis.